Epithelial mucins are glycoproteins with repetitive amino acid sequences and a high proportion of carbohydrates which are partially bound to membranes, partially secreted and are to be found on many glandular epithelia. The epithelial mucin known best is the membrane-bound MUC1, described also as PEM, PUM, EMA, MAM-6, PAS-0 or episialine (Finn, O. et al., Immunol. Reviews 145:61, 1995) the extracellular part of which consists of a variable number of repeating units of 20 amino acids, the so-called tandem repeats. The MUC1 is not a tumor specific molecule per se; its suitability as tumor antigen is based on the fact that its carbohydrate portion is qualitatively and quantitatively changed in tumors (Burchell, J. and Taylor-Papadimitriou, J., Epith. Cell Biol. 2:155, 1993). Here, new epitopes appear which are detected by the immune system (humoral and cellular defense).
After operatively removing the primary tumor (or after a radiation or chemotherapy) one, as a rule, has to proceed on the assumption that tumor cells still remain in the body (minimal residual disease). These tumor cells which represent a potential danger, are combated by various endogenic mechanisms the efficiency of which may be intensified by an adjuvant immunotherapy. The most effective adjuvant immunotherapy is vaccination. Here, two prerequisites are present: first, a suitable target antigen (epitope) has to be present on the tumor cells, and second that it should be possible to prepare a form of vaccine that is immunogenically as strong as possible, most suitably in a synthetic form.
Non-glycosylated oligo-repeat peptides of MUC1 represent a suitable target antigen in a number of frequently occurring carcinomas (Apostolopoulos, V. and McKenzie, I. F. C., Crit. Rev. Immunol. 14:293, 1994). The immunodominant region of MUC1 is the PDTRPAP motif which occurs on each tandem repeat. However, experiments carried out so far to develop a vaccine on the basis of an individual tandem repeat have not been successful. According to the present state of knowledge a minimum length of the peptide which will be reached only in 3-5 tandem repeats is required for achieving the immunogenic conformation of the peptide (Fontenot, J. D. et al., J. Biomol. Struct. Dyn. 13:245, 1995).